Neutral endopeptidase (NEP) is an enzyme responsible for the metabolism of atrial natriuretic peptide (ANP). Inhibition of NEP results in increased ANP concentrations, which in turn leads to natriuresis, diuresis and decreases in intravascular volume, venous return and blood pressure. ANP is released by atrial myocytes in response to atrial stretch. Elevated plasma concentrations of ANP have been demonstrated as a potential compensatory mechanism in various disease states, including congestive heart failure, renal failure, essential hypertension and cirrhosis. Accordingly, chronic monitoring of atrial stretch may be useful, e.g., for indirect monitoring of ANP concentration.
Heart failure (HF) is a condition in which a patient's heart works less efficiently than it should, resulting in the heart failing to supply the body sufficiently with the oxygen rich blood it requires, either at exercise or at rest. Congestive heart failure (CHF) is heart failure accompanied by a build-up of fluid pressure in the pulmonary blood vessels that perfuse the lungs. Transudation of fluid from the pulmonary veins into the pulmonary interstitial spaces, and eventually into the alveolar air spaces, is called pulmonary edema, and can cause shortness of breath, hypoxia, acidosis, respiratory arrest, and even death.
Chronic diseases such as CHF require close medical management to reduce morbidity and mortality. Because the disease status evolves with time, frequent physician follow-up examinations are typically necessary. At follow-up, the physician may make adjustments to the drug regimen in order to optimize therapy. This conventional approach of periodic follow-up is unsatisfactory for some diseases, such as CHF, in which acute, life-threatening exacerbations can develop between physician follow-up examinations.
Atrial Fibrillation (AF) is a very common supraventricular tachycardia (SVT) which leads to approximately one fifth of all strokes, and is the leading risk factor for ischemic stroke. However, AF is often asymptomatic and intermittent, which typically results in appropriate diagnosis and/or treatment not occurring in a timely manner.
It is believed that chronic monitoring of the pressures within the chambers of the heart will be important in future cardiac pulse generator applications. To monitor CHF status, clinicians ideally would like to know left ventricular end-diastolic pressure (LVEDP). However, it is rarely possible to directly measure LVEDP because of the invasiveness required of a transducer capable of making such a measurement. An alternative is to measure left atrial pressure (LAP) at a time when the pressure in the left atrium and left ventricle is the same, namely at the end of an atrial contraction, when the mitral valve (located between the left and right atrium) is still open.
There is also a desired to measure pulmonary capillary wedge pressure (PCWP). PCWP is typically measured by inserting balloon-tipped, multi-lumen catheter (Swan-Ganz catheter) into a peripheral vein, then advancing the catheter into the right atrium, right ventricle, pulmonary artery, and then into a branch of the pulmonary artery. Just behind the tip of the catheter is a small balloon that can be inflated with air (˜1 cc). The catheter has one opening (port) at the tip (distal to the balloon) and a second port several centimeters proximal to the balloon. These ports are connected to pressure transducers. When properly positioned in a branch of the pulmonary artery, the distal port measures pulmonary artery pressure (˜25/10 mmHg) and the proximal port measures right atrial pressure (˜0-3 mmHg). The balloon is then inflated, which occludes the branch of the pulmonary artery. When this occurs, the pressure in the distal port rapidly falls, and after several seconds, reaches a stable lower value that is very similar to left atrial pressure (normally about 8-10 mmHg). The balloon is then deflated. The same catheter can be used to measure cardiac output by the thermodilution technique. The pressure recorded during balloon inflation is similar to left atrial pressure because the occluded vessel, along with its distal branches that eventually form the pulmonary veins, acts as a long catheter that measures the blood pressures within the pulmonary veins and left atrium.
Measures of PCWP and/or LAP can be used to diagnose the severity of left ventricular failure and to quantify the degree of mitral valve stenosis. Both of these conditions elevate LAP and therefore PCWP. Aortic valve stenosis and regurgitation, and mitral regurgitation also elevate LAP and PCWP. When these pressures are sufficiently high, pulmonary edema may be present, which is a life-threatening condition. Note that LAP is the outflow or venous pressure for the pulmonary circulation and increases in LAP are transmitted almost fully back to the pulmonary capillaries thereby increasing their filtration.
Measures of PCWP can also be used to monitor pulmonary hypertension. Pulmonary hypertension is often caused by an increase in pulmonary vascular resistance. To calculate this, pulmonary blood flow (usually measured by the thermodilution technique), pulmonary artery pressure and PCWP measurements are typically required. Pulmonary hypertension can also result from increases in pulmonary venous pressure and pulmonary blood volume secondary to left ventricular failure or mitral or aortic valve disease.
PCWP is also useful in evaluating blood volume status when fluids are administered during hypotensive shock. One practice is to administer fluids at a rate that maintains PCWP within a desired range.
P-wave-duration (PWD) and P-wave-dispersion (Pd) in body surface electrocardiograms (ECGs) have been used by electro-physiologists (EPs) as noninvasive markers of intra-atrial conduction disturbances that predispose patients to AF. For example, an article by Yamada et al., entitled “Prediction of paroxysmal atrial fibrillation in patients with congestive heart failure: a prospective study,” (J Am Coll Cardiol 2000; 35:405-13), demonstrated that attacks of paroxysmal AF occurred more frequently in patients (32%) with an abnormal P-wave signal-average electrogram (P-SAECG) than in those without (2%) an abnormal P-SAECG. The Yamada et al. article also concluded that patient's with CHF who developed proxysmal AF had a significantly longer duration of signal-averaged P-wave in body surface ECGs than those without.
An article by Faggiano et al., entitled “Contribution of left atrial pressure and dimension to signal averaged P-wave duration in patients with chronic congestive heart failure” (Am J Cardiol 1997; 179:219-22), observed that in patient's with CHF, signal averaged P-wave duration in body surface ECGs increase with an increase in pulmonary capillary wedge pressure (PCWP).
Further, an article by Song et al., entitled “Effect of diuresis on P-wave duration and dispersion” (Pharmaco therapy 2002; 22:564-8), observed that signal averaged P-wave duration in body surface ECGs increase with an increase the presence of fluid overload during heart failure decompensation, and decrease with administration of diuretics.
There is also a desire to monitor right pulmonary artery pressure (RPAP), e.g., for the purpose of indirectly monitoring the hemodynamic response to fluid therapy, medication and other treatments. RPAP is typically measured using a balloon-tipped multi-lumen catheter, similar to the one described above.